Effects of sex hormones on Alzheimer's disease-associated β-amyloid oligomer formation in vitro

被引：29

作者：

Morinaga, Akiyoshi ^{[1
,2
]}

Ono, Kenjiro ^{[1
]}

Takasaki, Junichi ^{[1
]}

Ikeda, Tokuhei ^{[1
]}

Hirohata, Mie ^{[1
,2
]}

Yamada, Masahito ^{[1
]}

机构：

[1] Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol Aging, Kanazawa, Ishikawa 9208640, Japan

[2] Natl Hosp Org, Iou Hosp, Dept Neurol, Kanazawa, Ishikawa 9200192, Japan

来源：

EXPERIMENTAL NEUROLOGY | 2011年 / 228卷 / 02期

关键词：

Alzheimer's disease; Amyloid beta-protein; Oligomer; Photo-induced cross-linking of unmodified proteins; Electron microscopy; Estrogen; Central nervous systems; Sex hormones; ESTROGEN REPLACEMENT THERAPY; PHOTOINDUCED CROSS-LINKING; HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; PROTEIN OLIGOMERS; COGNITIVE FUNCTION; UNMODIFIED PROTEINS; OLDER WOMEN; DEMENTIA; AGGREGATION;

D O I：

10.1016/j.expneurol.2011.01.011

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The folding of amyloid beta-protein (A beta) into oligomeric, protofibrillar, and fibrillar assemblies is hypothesized to be the key pathogenic event in Alzheimer's disease (AD), with oligomeric assemblies thought to be the most neurotoxic. Inhibitors of oligomer formation, therefore, could be valuable therapeutics for patients with AD. Epidemiological studies have indicated that estrogen therapy reduces the risk of developing AD in women. Here, we examined the effects of estrogen (estrone (El), estradiol (E2), and estriol (E3)) and related sexual steroids (androstenedione (AND) and testosterone (TES)) on the in vitro oligomer formation of A beta(1-40) and A beta(1-42) using a method of photo-induced cross-linking of unmodified proteins (PICUP) and electron microscopic studies. Estrogens (E1, E2, and E3) inhibited low-order A beta oligomer formation, and among them, E3 had the strongest in vitro activity. Estrogen could be a potential therapeutic agent to prevent or delay AD progression, and further understanding of the fact that these very similar molecules have different anti-oligomeric effects would contribute to the development of new agents. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：298 / 302

页数：5

共 48 条

[11] Soluble protein oligomers in neurodegeneration:: lessons from the Alzheimer's amyloid β-peptide [J].